Evidence mapPaperPMID 41125636Full record

ArticleScientific reports2025

Fenofibrate differentially activates PPARα-mediated lipid metabolism in rat kidney and liver.

Venkat R Pannala, Michele R Balik-Meisner, Deepak Mav, Dhiral P Phadke, Elizabeth H Scholl, Ruchir R Shah, Warren Casey, Scott S Auerbach, Anders Wallqvist

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Venkat R PannalaDepartment of Defense Biotechnology High Performance Computing Software Applications Institute, Defense Health Agency Research & Development, Medical Research and Development Command, Fort Detrick, MD, 21702, USA. vpannala@bhsai.org.
Michele R Balik-MeisnerSciome LLC, Research Triangle Park, NC, 27709, USA.
Deepak MavSciome LLC, Research Triangle Park, NC, 27709, USA.
Dhiral P PhadkeSciome LLC, Research Triangle Park, NC, 27709, USA.
Elizabeth H SchollSciome LLC, Research Triangle Park, NC, 27709, USA.
Ruchir R ShahSciome LLC, Research Triangle Park, NC, 27709, USA.
Warren CaseyDivision of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
Scott S AuerbachDivision of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
Anders WallqvistDepartment of Defense Biotechnology High Performance Computing Software Applications Institute, Defense Health Agency Research & Development, Medical Research and Development Command, Fort Detrick, MD, 21702, USA. sven.a.wallqvist.civ@health.mil.

Funding

Scientific Cyberinfrastructure Research ProgramZIAES103385 · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · 2025 to 2025
$3.6M
NIEHS NIH HHS 27302C0031NIEHS NIH HHS ZIAES103385U.S. Army Medical Research and Development Command W81XWH20C0031
6 · The paper itself

Abstract

Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely prescribed to treat hyperlipidemia and has therapeutic potential in liver and kidney diseases. However, fenofibrate is also associated with adverse effects, including elevated creatinine and liver and kidney toxicity, although the underlying mechanisms remain unclear. In addition, how fenofibrate regulates lipid metabolism differently in the liver and kidney is not well understood. Therefore, in this study, we investigated the dose-dependent effects of fenofibrate on liver and kidney metabolism in rats, with a focus on PPARα activation and potential mechanisms contributing to organ-specific toxicity. We used high-throughput transcriptomic data from 5-day rat in vivo studies, where rats were exposed to fenofibrate, and performed pathway enrichment, injury module, and detailed individual gene comparison analyses to investigate how liver and kidney metabolism were differentially altered between the two organs. Fenofibrate exposure significantly increased liver but not kidney weights and caused larger perturbations in the liver compared to the kidney transcriptome, with the majority of the changes related to PPARα regulation. Interestingly, our study revealed that the PPARα and RXRα genes are differentially regulated between the liver and kidney. In addition, we identified several differences between them in cellular and mitochondrial fatty acid transport, lipoprotein metabolism, fatty acid oxidation, branched-chain amino acid degradation, and glucose metabolism pathways. Furthermore, we identified transcriptomic inflection points at which the changes in the PPARα-mediated regulation of lipid metabolism switched from beneficial to deleterious as the fenofibrate concentration increased leading to liver injury, providing potential mechanisms of toxicity.

Indexed as

FenofibrateKidneyLipid MetabolismLiverPPAR alphaAnimalsGene Expression RegulationHypolipidemic AgentsMaleRatsRats, Sprague-DawleyTranscriptomeFenofibrateHypolipidemic AgentsPPAR alphaBranched-chain amino acidsFatty acid uptakeFenofibrateGluconeogenesisLipid metabolismPeroxisomePPARα

Identifiers

PMID41125636
PMCPMC12546913

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.